One of the world's top ex­perts in coro­nary heart dis­ease is spear­head­ing a new gene edit­ing up­start out to trans­form the field

As head of the Cen­ter for Hu­man Ge­net­ic Re­search at Mass­a­chu­setts Gen­er­al Hos­pi­tal and the Broad’s Car­dio­vas­cu­lar Dis­ease Ini­tia­tive, Sekar Kathire­san has oc­cu­pied a sin­gu­lar po­si­tion as one of the world’s lead­ing ex­perts on the con­nec­tion be­tween ge­net­ics and coro­nary heart dis­ease. He’s tracked how peo­ple dealt a bad ge­net­ic hand — and the el­e­vat­ed risks that come with it — can lim­it in­her­ent dan­gers by lifestyle changes, and pon­dered over the ef­fects of dai­ly drugs used to treat mass pa­tient groups. And he’s reached a sim­ple con­clu­sion:

None of it is re­al­ly work­ing. 

In par­tic­u­lar, none of that is any­where near as use­ful as the ge­net­ic mu­ta­tions that he’s seen that con­fer a low­er risk of dy­ing and car­dio events. Par­tic­u­lar­ly the in­di­vid­u­als who car­ry mu­ta­tions “which break ei­ther of two genes — APOC3 or ANGPTL3 — rapid­ly clear triglyc­eride-rich lipopro­teins from the cir­cu­la­tion” and pro­tect them from heart at­tack.

Now, he’s mak­ing a pro­fes­sion­al leap to see if he and a squad of in­ves­ti­ga­tors at a new­ly launched biotech can dra­mat­i­cal­ly change the im­per­fect sta­tus quo through gene edit­ing.

“Imag­ine,” he tells me, “an in­jec­tion ad­min­is­tered once in life that safe­ly con­fers last­ing pro­tec­tion.”

No more pills. No fleet­ing com­mit­ments to healthy lifestyles that can’t stretch past Jan­u­ary. But a wide­spread and durable shar­ing of the same health ben­e­fits he’s seen in the very, very few. That’s the dream.

To­day, Kathire­san is step­ping down from his lofty aca­d­e­m­ic roles and mak­ing his de­but as CEO of Verve Ther­a­peu­tics, which is tak­ing its place in the hotbed of gene ther­a­py work around Cam­bridge, MA. The small team of 10 — soon to dou­ble in size — may not come close to ri­val­ing the big biotechs that oc­cu­py the streets in and around Har­vard and MIT. But rel­a­tive­ly few can claim the same kinds of con­nec­tions in the realms of drug sci­ence.

Ki­ran Musunuru

An­oth­er car­dio ge­net­ics ex­pert, Penn’s Ki­ran Musunuru and Har­vard pro­fes­sor J Kei­th Joung, who co-found­ed gene ther­a­py pi­o­neer Ed­i­tas, are on board as sci­en­tif­ic co-founders. There’s an al­liance with Beam Ther­a­peu­tics, the up­start next-gen gene edit­ing out­fit found­ed by Feng Zhang, one of 3 sci­en­tists wide­ly cred­it­ed with ush­er­ing in the CRISPR rev­o­lu­tion that has armed re­searchers around the world with ef­fec­tive tools to ac­com­plish their work. And Ver­i­ly will help work on the nanopar­ti­cles they plan to use for de­liv­ery.

Burt Adel­man, the for­mer EVP of R&D at Bio­gen, will chair the board, which in­cludes the Broad’s chief da­ta of­fi­cer, An­tho­ny Philip­pakis.

Beam will pro­vide some of the tech, and has an op­tion to step in on fu­ture com­mer­cial­iza­tion. Verve has al­so nailed down CRISPR patents, in­clud­ing Cas9 and Cas12a (Cpf1), from the Broad In­sti­tute and Har­vard Uni­ver­si­ty.

And they have $58.5 mil­lion in cash to do their work from GV (you prob­a­bly still think of them as Google Ven­tures), which is step­ping in with ARCH Ven­ture Part­ners, F-Prime Cap­i­tal, and Bio­mat­ics Cap­i­tal to form the orig­i­nal syn­di­cate.

To be suc­cess­ful, the Verve team un­der Kathire­san will not just have to demon­strate their ap­proach can safe­ly work, but al­so that it ul­ti­mate­ly can be done on a mass ba­sis in eco­nom­ic terms. That’s a tall or­der, but they do have some ad­van­tages, per­haps most no­tice­ably the ad­vances the ground­break­ers have made at the FDA, says the sci­en­tist.

“Gene edit­ing has the po­ten­tial to com­plete­ly trans­form the treat­ment par­a­digm for the dis­ease,” says Musunuru. “Pre­clin­i­cal stud­ies con­duct­ed in the field, in­clud­ing work done in my lab, have shown the promise of gene edit­ing to safe­ly re­duce cho­les­terol and oth­er coro­nary artery dis­ease risk fac­tors.”

So far, gene edit­ing in the le­git­i­mate R&D world has been cen­tered on the painstak­ing ad­vances of a hand­ful of pro­grams aimed at rare dis­eases. And Verve will start with its own rare ail­ments, tar­get­ing pa­tient pop­u­la­tions with the high­est un­met med­ical need. But Kathire­san isn’t drop­ping his pres­ti­gious aca­d­e­m­ic roles to search for mar­gin­al gains. He wants to tack­le the whole threat on a world­wide ba­sis.

That, of­fi­cial­ly, starts at Verve to­day.

UP­DAT­ED: In sur­prise switch, Bris­tol-My­ers is sell­ing off block­buster Ote­zla, promis­ing to com­plete Cel­gene ac­qui­si­tion — just lat­er

Apart from revealing its checkpoint inhibitor Opdivo blew a big liver cancer study on Monday, Bristol-Myers Squibb said its plans to swallow Celgene will require the sale of blockbuster psoriasis treatment Otezla to keep the Federal Trade Commission (FTC) at bay.

The announcement — which has potentially delayed the completion of the takeover to early 2020 — irked investors, triggering the New York-based drugmaker’s shares to tumble Monday morning in premarket trading.

Celgene’s Otezla, approved in 2014 for psoriasis and psoriatic arthritis, is a rising star. It generated global sales of $1.6 billion last year, up from the nearly $1.3 billion in 2017. Apart from the partial overlap of Bristol-Myers injectable Orencia, the company’s rival oral TYK2 psoriasis drug is in late-stage development, after the firm posted encouraging mid-stage data on the drug, BMS-986165, last fall. With Monday’s decision, it appears Bristol-Myers is favoring its experimental drug, and discounting Otezla’s future.

The move blindsided some analysts. Credit Suisse’s Vamil Divan noted just days ago:

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Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Fol­low­ing news of job cuts in Eu­ro­pean R&D ops, Sanofi con­firms it’s of­fer­ing US work­ers an 'ear­ly ex­it'

Ear­li­er in the week we learned that Sanofi was bring­ing out the bud­get ax to trim 466 R&D jobs in Eu­rope, re­tool­ing its ap­proach to car­dio as re­search chief John Reed beefed up their work in can­cer and gene ther­a­pies. And we’re end­ing the week with news that the phar­ma gi­ant has al­so been qui­et­ly re­duc­ing staff in the US, tar­get­ing hun­dreds of jobs as the com­pa­ny push­es vol­un­tary buy­outs with a fo­cus on R&D sup­port ser­vices.

Gene ther­a­py biotech sees its stock rock­et high­er on promis­ing re­sults for rare cas­es of but­ter­fly dis­ease

Shares of Krys­tal Biotech took off this morn­ing $KRYS af­ter the lit­tle biotech re­port­ed promis­ing re­sults from its gene ther­a­py to treat a rare skin dis­ease called epi­der­mol­y­sis bul­losa.

Fo­cus­ing on an up­date with 4 new pa­tients, re­searchers spot­light­ed the suc­cess of KB103 in clos­ing some stub­born wounds. Krys­tal says that of 4 re­cur­ring and 2 chron­ic skin wounds treat­ed with the gene ther­a­py, the KB103 group saw the clo­sure of 5. The 6th — a chron­ic wound, de­fined as a wound that had re­mained open for more than 12 weeks — was par­tial­ly closed. That brings the to­tal so far to 8 treat­ed wounds, with 7 clo­sures.

Evotec CEO Werner Lanthaler, File Photo

Ox­ford, Evotec ramp up LAB10x with AI ex­perts at Sen­syne — fo­cused on biotech spin­outs

Ox­ford is al­ly­ing it­self with Evotec and ar­ti­fi­cial in­tel­li­gence out­fit Sen­syne Health to ramp up some new biotech spin­outs while look­ing to “ac­cel­er­ate da­ta-dri­ven drug dis­cov­ery and de­vel­op­ment.”

The big idea here is that Ox­ford sci­en­tists — some of the best drug hunters in the world — can uti­lize Sen­syne’s AI plat­form for their work, re­ly­ing on the chemists and hands-on de­vel­op­ers at Evotec to push ahead to a crit­i­cal proof of con­cept mo­ment. And they’ll do it through a project leader called LAB10x, which gets £5 mil­lion over the next three years to fund the work.

Suf­fer­ing No­var­tis part­ner Cona­tus is pack­ing it in on NASH af­ter a se­ries of un­for­tu­nate tri­al events

The NASH par­ty is over at No­var­tis-backed Cona­tus. And this time they’re turn­ing off the lights.

More than 2 years af­ter No­var­tis sur­prised the biotech in­vest­ment com­mu­ni­ty with its $50 mil­lion up­front and promise of R&D sup­port to part­ner with the lit­tle biotech on NASH — ig­nit­ing a light­ning strike for the share price — Cona­tus $CNAT is back with the lat­est bit­ter tale to tell about em­ri­c­as­an, which once in­spired con­fi­dence at the phar­ma gi­ant.

Dean Hum. Nasdaq via YouTube

Gen­fit goes to Chi­na with a deal worth up to $228M for NASH drug

Fresh off the high of its Nas­daq IPO de­but, and the low of com­par­isons to Cymabay — whose NASH drug re­cent­ly stum­bled — Gen­fit on Mon­day un­veiled an up to $228 mil­lion deal with transpa­cif­ic biotech Terns Phar­ma­ceu­ti­cals to de­vel­op its flag­ship ex­per­i­men­tal liv­er drug — elafi­bra­nor — in Greater Chi­na.

The deal comes weeks af­ter Gen­fit $GN­FT is­sued a fiery de­fense of its dual PPAR ag­o­nist elafi­bra­nor, when com­peti­tor Cymabay’s PPARδ ag­o­nist, se­ladel­par, fiz­zled in a snap­shot of da­ta from an on­go­ing mid-stage tri­al. The main goal at the end of 12 weeks was for se­ladel­par to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in liv­er fat con­tent, but da­ta showed that pa­tients on the place­bo ac­tu­al­ly per­formed bet­ter.

Alex­ion wins pri­or­i­ty re­view for Ul­tomiris' aHUS in­di­ca­tion; FDA ex­pands ap­proval of Ver­tex's Symdeko

→ Alex­ion $ALXN has scored a speedy re­view for Ul­tomiris for pa­tients with atyp­i­cal he­molyt­ic ure­mic syn­drome (aHUS) af­ter post­ing pos­i­tive da­ta from a piv­otal study in Jan­u­ary. The drug is the rare dis­ease com­pa­ny’s shot at pro­tect­ing its block­buster blood dis­or­der fran­chise that is cur­rent­ly cen­tered around its flag­ship drug, Soliris, which is a com­ple­ment in­hibitor typ­i­cal­ly ad­min­is­tered every two weeks. Ul­tomiris has a sim­i­lar mech­a­nism of ac­tion but re­quires less-fre­quent dos­ing — every eight weeks. The de­ci­sion date has been set to Oc­to­ber 19. Late last year, Ul­tomiris se­cured ap­proval for noc­tur­nal he­mo­glo­bin­uria (PNH) pa­tients.

Bet­ter than Am­bi­en? Min­er­va soars on PhI­Ib up­date on sel­torex­ant for in­som­nia

A month af­ter roil­ing in­vestors with what skep­tics dis­missed as cher­ry pick­ing of its de­pres­sion da­ta, Min­er­va is back with a clean slate of da­ta from its Phase IIb in­som­nia tri­al.

In a de­tailed up­date, the Waltham, MA-based biotech said sel­torex­ant (MIN-202) hit both the pri­ma­ry and sev­er­al sec­ondary end­points, ef­fec­tive­ly im­prov­ing sleep in­duc­tion and pro­long­ing sleep du­ra­tion. In­ves­ti­ga­tors made a point to note that the ef­fects were con­sis­tent across the adult and el­der­ly pop­u­la­tions, with the lat­ter more prone to the sleep dis­or­der.